The Role Of CaN/NFAT Signaling Pathway In Aerobic Exercise-induced Imoroyment Of Blood Vessel Function In Hypertension

Purpose: CaN/NFAT signaling plays an indispensable role in regulating vascular smooth muscle cell contraction and relaxation.This researth wants to investigate the mechanism of CaN/NFAT signaling pathway underlying the reversal effect of aerobic exercise on the hypertension-induced mesenteric artery remodeling.Methods: Male spontaneously hypertensive rats(SHRs)and Wistar-Kyoto rats(WKYs),12 weeks age,were randomly separated into a sedentary group(WKY-SED,SHR-SED),and an exercise group(WKY-EX,SHR-EX).WKY-SED and SHR-SED were used as normotensive control.Exercise groups were subjected to a 12-week treadmill training protocol: 20m/min(about 55-65% of maximal aerobic velocity),0% grade,60min/day,5d/w.After 12 weeks,body weight,heart rate and blood pressure was acquired of each group.Immunohistochemical was used to observe the distribution and changing of KV2.1 and CaN in mesenteric artery(MA).Western blot was applied to examine the expression levels of KV2.1,CaN,NFAT,p-NFAT,AKAP150 and CaM protein in MA.cell immunofluorescence was perfomed to study the space distribution and co-localization of CaN and AKAP150 in vascular smooth muscle cell.Results:(1)No significant differences were observed in body weights(BW),heart rate(HR)and blood pressure(BP)before exercise;after 12 weeks,HR,systolic blood pressure(SBP),diastolic blood pressure(DBP)and mean arterial pressure(MBP)in SHR-SED group was significantly higher than that in WKY-SED(P<0.01);after exercise,BW,HR,SBP and MBP in SHR-EX was significantly lower than that in SHR-SED(P<0.01),BW and SBP in WKY-EX group was lower than WKY-SED(P<0.01).(2)the positive immunoactivity of KV2.1 protein in SHR-SED group was significantly lower than WKY-SED(P < 0.01),while the CaN protein was significantly increased in SHR-SED compared to WKY-SED(P<0.01);after 12 weeks,exercise training markedly increased the KV2.1 expression in MA(P <0.01),and inhibited the expression of CaN in SHR-EX(P<0.01).(3)the protein expression of CaN,AKAP150 and CaM in SHR-SED group was significantly higher than that of WKY-SED(P<0.01),the protein expression of p-NFAT and KV2.1 in SHR-SED group were significantly lower than in WKY-SED(P<0.01);aerobic exercise dramaticlly decreased the upregulation protein expression of CaN,AKAP150 and CaM in bypertension(P < 0.01),while increased the protein expression of p-NFAT and KV2.1 in SHR-EX group(P<0.01);WKY-SED and WKY-EX group had no significant difference.(4)Vascular smooth muscle cells expressed CaN and AKAP150 protein;CaN was located in the arterial myocyte plasma membrane and cytoplasm,AKAP150 was mainly present at the cell surface.Conclusions: The increased CaN/NFAT signaling pathway may induce the KV2.1 expression down,however,aerobic exercise can effectively inhibit this down,which maybe the mechanism of exercise reversing hypertension induced pathological change and restoring mesenteric arterial function.